P712: ASCIMINIB ITALIAN MANAGED ACCESS PROGRAM: EFFICACY PROFILE IN HEAVILY PRE-TREATED CML PATIENTS
Authors: M. Breccia, A. V. Russo Rossi, B. Martino, E. Abruzzese, M. Annunziata, G. Binotto, A. Ermacora, C. Fava, L. Giaccone, V. Giai, A. P. Nardozza, P. Coco, A. Gozzini, L. Levato, A. Lucchesi, L. Luciano, M. Maria Cristina, G. Rege-Cambrin, M. Santoro, B. Scappini, A. R. Scortechini, P. Sportoletti, E. Trabacchi, F. Castagnetti
Journal: HemaSphere (2022)

Background: Chronic myeloid leukemia (CML) patients who have experienced failure and/or intolerance to multiple lines of treatment have limited therapeutic possibilities. Novel treatment options are needed to achieve sustained responses and increased tolerability in this subset of patients. Asciminib, unlike all approved tyrosine kinase inhibitors (TKIs) that bind to the ATP site of the BCR-ABL1 oncoprotein, is an allosteric, first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor with a new mechanism of action that has shown efficacy in heavily pre-treated patients after two TKIs or more. Aims: We share our experience on asciminib use in CML patients outside of clinical trials. Methods: We describe retrospective data from 34 chronic phase CML patients in their 3rd or later line, treated with asciminib between April 2019 and October 2021 in 22 Italian institutions. The drug was granted by Novartis under a Managed Access Program (MAP). BCR::ABL1/ABL ratio was expressed as % IS in all centers. Efficacy was analyzed by comparing the response registered at the latest time point (34 pts evaluable) or at 3 months (27 pts evaluable – we excluded those patients for whom molecular analysis was not assessed) vs the response at baseline. Patient recruitment, dosing regimen and safety were recorded according to the MAP recommendations. The safety information was extracted from Argus database, a Novartis database where all adverse events related to Novartis compounds are stored. Results: Median time of asciminib treatment was 8.3 months (3.3–33.2) for the whole cohort. Patients' characteristics are displayed on Fig 1. Twenty-five patients (73.5%) were pretreated with at least 3 or more TKIs and 50% have reported to have ≥3 comorbidities. Approximately 59% of patients received prior ponatinib. Switch to asciminib occurred for resistance in 21 pts (61.8%) and intolerance in 10 pts (29.4%). Ten patients (29.4%) harbored mutations in ABL kinase domain, and 5 (14.7%) have a T315I mutation. All the T315I patients had a previous ponatinib exposure. Nineteen out of 27 (70.4%), 12/27 (44.4%) and 6/27 (22.2%) achieved or maintained respectively Molecular Response of 2 log reduction (MR2), Major Molecular Response (MMR) and Deep Molecular Response (DMR) at three months' time point. Twenty-four out of 34 (70.5%), 14/34 (41.7%) and 8/34 (23.5%) achieved or maintained respectively MR2, MMR, DMR response at the last follow up. After 3 months and at the last follow up, 18/27 (66.7%) and 20/34 (58.8%) of patients, respectively, showed an improvement of previous baseline response. Approximately 37% and 35%, without MMR response at baseline, reached at least an MMR at three months and last follow up, respectively. We also observed that ponatinib treated patients showed a reduced probability of reaching MR2, MMR and DMR responses compared to ponatinib naive patients at both 3 months and last follow up time points. Seventy-five percent of patients with a T315I mutation showed a response improvement, respect to baseline, already after 3 months on asciminib. The safety profile of asciminib, based on the information spontaneously reported by physicians, remained consistent with that already reported, with no new safety findings. Image:Summary/Conclusion: Asciminib has shown a promising efficacy profile and tolerability in a setting of CML patients resistant and/or intolerant to 2 or more TKIs and with a high comorbidity burden. Our results confirmed what observed in sponsored trials and in the other world-wide programs, strongly suggesting a possible role for this new agent in the future therapeutic scenario.